What the Brain Tells the Spinal Cord: Lamina I/III NK1-Expressing Neurons Control Spinal Activity via Descending Pathways

摘要

The long-term increase in pain sensitivity that frequently follows tissue or nerve injury is thought to be due to alterations in synaptic transmission and morphology within the spinal cord and to changes in descending controls from the brainstem (Hunt and Mantyh 2001). Neurokinin-1 (NK1) receptors, which are highly expressed in the superficial dorsal horn, form part of several important ascending pathways. Although NK1-expressing lamina I neurons make collateral projections to the deeper dorsal horn (Light et al. 1993; Cheunsuang and Morris 2000), they are also predominantly nociceptive-specific projection neurons terminating extensively within the parabrachial area (PB), with other terminations in the periaqueductal gray area, thalamus, and reticular formation (Todd et al. 2000; Gauriau and Bernard 2002; Lima and Almeida 2002). The PB accesses areas of the brain such as the amygdala and hypothalamus that modulate descending monoaminergic pathways from the brainstem and regulate nociceptive processing at spinal levels (Hunt 2000). Input from the periphery is therefore under continuous modulation by descending influences from the brainstem and intrinsic spinal mechanisms. We have used the molecular microneurosurgical technique of substance P/saporin (SP-SAP) to ablate lamina I and/or III (I/ III) NK1 projection neurons (Mantyh et al. 1997) and show their significant effect on both descending controls and local spinal circuits.